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サイトウ ミネキ
Mineki Saito
齊藤 峰輝 所属 川崎医科大学 医学部 基礎医学 微生物学 職種 教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Dysregulation of the tumor suppressor Menin and its target Bach2 in HTLV-1 infection. |
| 掲載誌名 | 正式名：Retrovirology 略 称：Retrovirology ISSNコード：17424690/17424690 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 22(1),pp.3 |
| 著者・共著者 | Hiroe Sejima, Tadasuke Naito, Takuya Fukushima, Mineki Saito |
| 担当区分 | 最終著者,責任著者 |
| 発行年月 | 2025/03/25 |
| 概要 | BACKGROUND:The tumor suppressor Menin, prone to mutations in both hereditary and sporadic endocrine tumors, along with its direct target Bach2, plays a crucial role in preventing autoimmunity by regulating CD4 + T cell senescence and maintaining cytokine homeostasis. Since human T-cell leukemia virus type 1 (HTLV-1) primarily infects CD4 + T cells, and its dysregulation contributes to both the hematological malignancy of adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we examined the involvement of the Menin-Bach2 pathway in HTLV-1 infection.METHODS:The mRNA expression of menin and bach2 in HTLV-1-infected and uninfected human T-cell lines, peripheral blood mononuclear cells (PBMCs) from patients with ATL, HAM/TSP, and asymptomatic carriers were analyzed. Additionally, interactions between Menin or Bach2 and the Tax or HBZ; the subcellular localization of these proteins; the effect of knockdown of menin, tax, and HBZ genes; and the effects of interaction inhibitors between menin and its cofactor, mixed lineage leukemia (MLL), on the proliferation of HTLV-1-infected T cells were evaluated.RESULTS:The findings were as follows: (1) In all eight HTLV-1-infected T-cell lines tested, Menin protein was expressed, whereas Bach2 expression was absent in five of them; (2) the mRNA levels of both menin and bach2 significantly decreased in PBMCs from patients with HAM/TSP and ATL; (3) Tax and HBZ each physically interacted with both Menin and Bach2; (4) knockdown of tax, but not HBZ, downregulated Bach2, but not Menin expression in HTLV-1-transformed T-cell lines MT-2 and SLB-1; (5) knockdown of menin downregulated Bach2 expression in MT-2 but not in SLB-1; (6) A Menin-MLL interaction inhibitor suppressed cell growth of MT-2 but not in SLB-1; (7) HBZ and Menin exhibited different subcellular localization between MT-2 and SLB-1.CONCLUSIONS:HTLV-1 infection alters the regulation of the Menin-Bach2 pathway, which contro |
| DOI | 10.1186/s12977-025-00660-7 |
| PMID | 40128849 |